Fusion Pore

Introduction

Exocytosis is a universal process of eukaryotic cells. This activity of cells consists of fusion between the plasma membranes and the vesicle, leading to the formation of a fusion pore. Fusion pore is the aqueous pathway by which molecules leave a vesicle and move out into the surrounding extracellular region. A fusion pore is relatively narrow. However, when it forms, it can expand to allow the vesicle membrane to merge with the plasma membrane. As shown in Figure 1, state 2b could be regarded as a closed fusion pore, which could open to a proteinaceous pore (state 3). A lipidic fusion pore (state 5) is an essential intermediate in any model of membrane fusion.

Fig.1 Putative intermediates of membrane fusion and their transitions. (Chang, 2017)

Transport Properties

Fusion pore provides a conduit for transport, and most of what we know about fusion pore derives from measurements of some form of flux. The transport of signaling molecules, ions, and membranes can be measured and used to gain insight into fusion pore structure and composition. Besides, it has been reported that patch clamp measurements of conductance and amperometry measurements of content flux could be used to illustrate successive stages of membrane fusion.

Composition and Structure

Secretion of neurotransmitters via exocytotic fusion pores is extremely necessary for synaptic transmission. Unfortunately, the ephemeral nature of fusion pores has severely limited efforts to study their composition and structure. During the past ten years, two asymmetric types of fusion pores have been observed.

• Rim-pores formed at the rim of a single membrane thick hemi-fusion diaphragm
• Vertex fusion pores formed at the edge or vertex of the contact zone formed during protein-mediated docking and adhesion of membranes

Efforts in structure research have also never ceased. Scientists developed an assay in which nanodiscs bearing v-SNAREs fuse with small unilamellar vesicles (SUVs) containing t-SNAREs, in a manner accelerated by Ca²⁺ and synaptotagmin-1. Finally, the study reveals that the fusion pore is formed by a combination of lipids and SNARE transmembrane domains.

Figure 2 The nanodisc-SUV fusion system to study fusion pores. (Bao, 2016)

Newly Research

In 2021, the scientist presented an in vitro method and studied the initial phase of vesicle fusion by three-dimensional (3D) microfluidic chip. They monitored the fusion of small vSNARE-decorated vesicles with a suspended asymmetric membrane containing tSNAREs and having the same lipid composition as a typical plasma membrane. Scientists finally identified three fusion pore stages: two reversible phases in which the fusion pore has an apparent diameter of 0.4 ± 0.1 nm and 0.8 ± 0.2 nm, and an irreversible phase above 1.5 nm where the fusion pore expands continuously and indefinitely.

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References

1. Chang, C. W. Fusion pores and their control of neurotransmitter and hormone release. Journal of General Physiology. 2017, 149(3): 301-322.
2. Bao, H.; et al. Exocytotic fusion pores are composed of both lipids and proteins. Nature structural & molecular biology. 2016, 23(1): 67.